Modified Ultrafiltration in Pediatric Heart Surgery

Historical Background

In 1974 Silverstein et al. modified the extracorporeal dialytic circuit by introducing an additional filter that could eliminate water and proteins with a molecular weight lower than 50,000 daltons (Da). With this modification, ultrafiltration could be used to treat conditions of chronic water retention or pulmonary edema; the filtration circuit was designed to be separate from and independent of the dialysis circuit. In 1979, Darup et al. applied hemofiltration to CPB in 10 patients with reduced or borderline kidney function undergoing cardiac surgery. During the 1980s, ultrafiltration was used as an adjunct to CBP only in patients with preoperative renal failure or edema. The concept of ultrafiltration arose as a response to the observation of an accumulation of total body water associated with open heart surgery. In the later 1980s and early 1990s, the hypothesis that tissue edema was causing organ dysfunction postoperatively stimulated the idea that removal of water from the body at the end of CPB would result in improved organ function and perhaps better outcomes. Introduction of ultrafiltration during and after CPB came right after this recognition. Naik et al. in 1991 were the first to report results with the use of modified ultrafiltration (MUF) in pediatric patients. Their randomized study, which included 50 children, showed that this technique decreased the need for blood products and colloids, reduced the amount of body fluid, and improved postoperative cardiac function. Several later studies have confirmed these results.

Inflammatory Response to Cardiopulmonary Bypass

It is widely known that CPB in cardiac surgery unleashes a broad and intense acute inflammatory response of variable degree, which, together with microembolization, is responsible for most of the morbidity of CPB. The inflammatory response to CPB is initiated by contact between heparinized blood and nonendothelial cell surfaces, with continuous recirculation of blood that is sequentially in contact with the wound, the perfusion circuit, and the intravascular compartment, to which is added the washout from reperfused ischemic organs and tissues. Blood contact with nonendothelial cell surfaces in the wound and in the perfusion circuit activates plasma zymogens and cellular blood elements that constitute part of the body's defense reaction to all noxious substances (including infectious agents, toxins, foreign antigens, allergens) and injuries. All surgery, like traumatic injury, triggers an acute inflammatory response, but the continuous exposure of heparinized blood to nonendothelial cell surfaces followed by reinfusion and circulation within the body greatly magnifies this response in procedures in which CPB is used.

Although far from fully elucidated, this predominantly “blood” injury is known to produce a unique response that differs from that caused by other threats to homeostasis. The principal blood elements involved in this acute defense reaction are contact and complement plasma protein systems, neutrophils, monocytes, endothelial cells, and, to a lesser extent, platelets. When activated during CPB, the principal blood elements release vasoactive and cytotoxic substances; produce cell signaling inflammatory and inhibitory cytokines; express complementary cellular receptors that interact with specific cell signaling substances and other cells; and generate a host of vasoactive and cytotoxic substances for release into the circulation. Blood circulating during clinical cardiac surgery with cardiopulmonary bypass is a stew of vasoactive and cytotoxic substances, activated blood cells, and microemboli. Shear stress, turbulence, cavitation, and other rheologic forces and complement components cause hemolysis of some red cells. Complement anaphylatoxins, bradykinin formed by activation of the contact proteins, and proinflammatory cytokines stimulate endothelial cells to contract, allowing extravasation of intravascular fluid into the extravascular space. As neutrophils and monocytes migrate across the endothelial cell barrier, stromal and parenchymal cells are exposed to a cytotoxic environment mediated by neutral proteases, collagenases, and gelatinases, reactive oxidants, lipid peroxides, complement components, and other cytotoxins.

The clinical manifestations of the inflammatory response include systemic signs and symptoms such as malaise, fever, increased heart rate, mild hypotension, interstitial fluid accumulation, and temporary organ dysfunction, particularly of the brain, heart, lungs, and kidneys. The magnitude of this defense reaction during and after CPB is influenced by many exogenous factors, including the surface area of the perfusion circuit, the duration of blood contact with extravascular surfaces, general health and preoperative organ function of the patient, extent of blood loss and replacement, organ ischemia and reperfusion injury, sepsis, different degrees of hypothermia, periods of circulatory arrest, the patient's genetic profile, and use of corticosteroids or other pharmacologic agents. Several methods have been proposed to control the acute inflammatory response to CBP such as off-pump cardiac surgery, maintenance of a perfusion temperature between 32°C and 34°C, utilization of perfusion circuit coatings with ionic- or covalent-bonded heparin, complement inhibitors, administration of glucocorticoids, and protease inhibitors such as aprotinin. The efficacy of these techniques as effective antiinflammatory approaches remains essentially unresolved and strictly linked to institutional protocols.